Fragment analogs as better mimics of obestatin

Regulatory Peptides
ShreeRanga NagarajUma V Manjappara

Abstract

Obestatin is a twenty three amino acid peptide produced in the stomach by post translational modification of the preproghrelin gene. Since its discovery in 2005, many studies have shown that obestatin reduces feed intake and gain in body weight in rodents. Studies from our laboratory have shown the N-terminal thirteen residues mimic obestatin the best and residues 6-18 reduce epididymal fat significantly in adult male mice. In this study we have tried to increase the efficacy of these fragments. As an initial step, we have substituted G(8) with alpha-aminoisobutyricacid(Aib,U) and F(5) with cyclohexylalanine(Cha) in the N-terminal peptide to obtain two modified peptides and modified the middle fragment (residues 6-18) by substituting both the glycine residues at position 3 and 8 with alpha-aminoisobutyricacid(U). The rationale being, unusual amino acids could protect the peptides from immediate degradation and Aib would also induce secondary structure in these unstructured peptides. The N-terminal fragment with the G(8)U substitution fared the best. It reduced food intake, gain in body weight, levels of cholesterol and triglycerides in the blood, epididymal and perirenal fat in adult male mice similar to that of obestatin. The ...Continue Reading

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Dec 18, 2007·Biochemical and Biophysical Research Communications·ShreeRanga NagarajUma V Manjappara

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Citations

Jan 5, 2014·Doklady Biological Sciences : Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections·E E KhirazovaA A Kamenskii
Jan 10, 2012·Peptides·Bart De SpiegeleerJuan Carlos Solis-Sainz
Apr 5, 2011·Molecular and Cellular Endocrinology·Inge SeimLisa Chopin
Jun 18, 2010·Peptides·Anusha P SubasinghageChandralal M Hewage
Jun 18, 2014·The International Journal of Biochemistry & Cell Biology·ShreeRanga NagarajUma V Manjappara
May 28, 2019·Cell Biochemistry and Biophysics·Musunuru Suneel Kumar Reddy, Uma V Manjappara

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